Risk factors for dental findings of the development of medication-related osteonecrosis of the jaw: Investigation of 3734 teeth in cancer patients receiving high dose antiresorptive agents.

Background/purpose: Local infection is a risk factor for medication-related osteonecrosis of the jaw (MRONJ), along with invasive dental treatment of the bone; the tooth that is the source of infection should be extracted prior to the administration of bone resorption inhibitors. However, which teeth should be extracted remains unclear. This study aimed to determine the relationship between dental findings prior to high-dose antiresorptive agent (ARA) administration and the subsequent development of MRONJ. Materials and methods: Patients with cancer who were scheduled to receive high-dose ARAs and referred to our hospital between 2011 and 2020 were included in this retrospective study. Apical lesions, enlargement of the periodontal space, thickening of the lamina dura, alveolar bone resorption of >1/3, periapical osteosclerosis, and local infection symptoms in each tooth were investigated using medical records and panoramic radiographs. Results: A total of 172 patients, 329 jaws, and 3734 teeth were registered. MRONJ developed in 68 teeth in 33 jaws of 32 patients. In tooth-by-tooth analysis, fewer teeth (P < 0.001), apical lesions (P < 0.001), periapical osteosclerosis (P < 0.001), local infection symptoms (P = 0.002), and one or more dental findings (P < 0.001) were significant factors for MRONJ development. In jaw-by-jaw analysis, old age, local infection symptoms, and number of radiographic abnormalities per tooth were significant. In patient-by-patient analysis, patients with diabetes and those with fewer teeth developed MRONJ. Conclusion: Patients with fewer teeth, apical lesions, periapical osteosclerosis, and local infection were more likely to develop MRONJ. Therefore, these teeth should be treated as much as possible before ARA administration.

Cellular dynamics of distinct skeletal cells and the development of osteosarcoma.

Bone contributes to the maintenance of vital biological activities. At the cellular level, multiple types of skeletal cells, including skeletal stem and progenitor cells (SSPCs), osteoblasts, chondrocytes, marrow stromal cells, and adipocytes, orchestrate skeletal events such as development, aging, regeneration, and tumorigenesis. Osteosarcoma (OS) is a primary malignant tumor and the main form of bone cancer. Although it has been proposed that the cellular origins of OS are in osteogenesis-related skeletal lineage cells with cancer suppressor gene mutations, its origins have not yet been fully elucidated because of a poor understanding of whole skeletal cell diversity and dynamics. Over the past decade, the advent and development of single-cell RNA sequencing analyses and mouse lineage-tracing approaches have revealed the diversity of skeletal stem and its lineage cells. Skeletal stem cells (SSCs) in the bone marrow endoskeletal region have now been found to efficiently generate OS and to be robust cells of origin under p53 deletion conditions. The identification of SSCs may lead to a more limited redefinition of bone marrow mesenchymal stem/stromal cells (BM-MSCs), and this population has been thought to contain cells from which OS originates. In this mini-review, we discuss the cellular diversity and dynamics of multiple skeletal cell types and the origin of OS in the native in vivo environment in mice. We also discuss future challenges in the study of skeletal cells and OS.